Attentional bias to alcohol cues in rats: development and decline

描述(由申请人提供)：人类对酒精相关刺激(酒精暗示)的关注是使用注意力偏差程序进行评估的，(A)可能会干扰酗酒者的其他活动，(B)与问题饮酒的模式和严重程度有关，(C)目前饮酒者的ND(C)比恢复中的人更严重。这一证据表明，减少对酒精线索的注意偏差的治疗可能会防止线索诱导的复发。相反，有效的治疗方法也可能通过促进禁欲来减少注意力偏向。更好地理解引起注意偏向变化的机制可以阐明注意偏向与复发之间的关系。这样的研究将由注意力偏向的临床前模型来促进。在这里，我们开发了一个人类注意偏差过程的动物模型，其中对酒精线索的关注干扰了目标的识别。在这个项目中，训练大鼠注意发出信号的刺激以及何时对食物做出反应(食物刺激)。刺激的呈现很简短，错误或遗漏的反应会被扣下食物奖励作为惩罚。一旦大鼠学会了这一系列反应时间(SRT)任务，我们就会在不同的会话中将音调(酒精线索)与酒精传递配对。 最终，在SRT过程中，大鼠将注意到酒精线索，但不会注意另一个(对照线索)，这将从酒精与对照线索呈现期间正确反应的潜伏期相对增加以及不正确或遗漏的反应中可见一斑。我们首先确定了增加SRT任务的注意需求如何通过减少食物刺激呈现的持续时间来影响酒精提示呈现的效果(目标1)。这为后续研究提供了参数优化。然后，我们考察了增加酒精+酒精线索配对会话的数量如何通过酒精线索呈现影响SRT成绩(目标2)。这与人类文献显示重度饮酒者与偶尔饮酒者之间存在更大的注意力偏向是一致的。最后，我们通过酒精线索呈现(目标3)来确定消退(在没有酒精的情况下呈现酒精线索)如何影响SRT成绩的干扰。我们将这些结果与匹配的暂停暴露时间(既没有酒精也没有线索)的大鼠的结果进行了比较。这将解决减少对酒精线索的注意偏差的治疗是否可以通过减少对熟悉环境中遇到的酒精线索的关注来防止复发，然后加速复发。不针对酒精暗示而只是强制戒酒的治疗可能不会提供这种额外的保护。这些实验建立了一种新的、创新的、可翻译的临床前注意偏差程序模型。这将为今后的研究提供便利 将注意偏向的临床观察与条件方法或仪器反应的临床前观察联系起来。这些研究还将促进未来对酒精提示注意力偏差的神经生物学机制的研究，并可能找到更有效的治疗方法来防止复发。

DESCRIPTION (provided by applicant): Attending to alcohol-associated stimuli (alcohol cues) is assessed in humans using attentional bias procedures and (a) can interfere with other activities in heavy drinkers, (b) is related to the pattern and severity of problematic drinking, nd (c) is greater among current drinkers versus those in recovery. This evidence suggests that therapies that decrease attentional bias to alcohol cues might prevent cue-induced relapse. Conversely, it is also possible that effective therapies decrease attentional bias by facilitating abstinence. Better understanding the mechanisms responsible for changes in attentional bias could elucidate the relationship between attentional bias and relapse. Such research would be facilitated by a preclinical model of attentional bias. Here we develop an animal model of the human attentional bias procedure, where attending to alcohol cues interferes with the identification of a target. In this project, rats are trained to attend to stimuli that signal whee and when to respond for food (food stimuli). Stimulus presentation is brief, and incorrect or omitted responses are penalized by withholding food reward. Once rats learn this serial reaction time (SRT) task, we pair a tone (alcohol cue) with alcohol delivery in separate sessions. Ultimately, rats will attend to the alcohol cue, but not another (control cue) during an SRT session, which will be evident from a relative increase in latency to correct responses and in incorrect or omitted responses during alcohol versus control cue presentation. We first determine how increasing the attentional demand of the SRT task influences the effect of alcohol cue presentation by decreasing the duration of the food stimuli presentations (Aim 1). This allows parameter optimization for subsequent studies. We then examine how increasing the number of alcohol + alcohol-cue pairing sessions affects interference with SRT performance by alcohol cue presentation (Aim 2). This would be consistent with human literature demonstrating greater attentional bias among heavier versus occasional drinkers. Finally, we determine how extinction (where the alcohol cue is presented without alcohol) affects interference with SRT performance by alcohol cue presentation (Aim 3). We compare these results to those from rats with a matched period of suspended exposure (where neither alcohol or the cue are present). This will address whether treatments that decrease attentional bias to alcohol cues might provide protection against relapse by reducing attention to alcohol cues encountered in familiar environments and then precipitate relapse. Treatments that do not target attending to alcohol cues but instead only impose abstinence may not provide this additional protection. These experiments establish a novel, innovative, and translational preclinical model of the clinical attentional bias procedure. This will facilitate future studies relating clinical observations of attentional bias to preclinical observations of conditioned approach or instrumental responding. These studies will also facilitate future investigation of neurobiological mechanisms of attentional bias to alcohol cues and could identify more effective therapies to prevent relapse.